Synapses are specialized cell adhesions that are the fundamental functional units of the nervous system, and they are generated during development with amazing precision and fidelity. During synaptogenesis, synapses form, mature, and stabilize and are also eliminated by a process that requires intimate communication between pre- and postsynaptic partners. In addition, there may be environmental determinants that help to control the timing, location, and number of synapses.
Synapses occur between neuron and neuron and, in the periphery, between neuron and effector cell, e.g. muscle. Functional contact between two neurons may occur between axon and cell body, axon and dendrite, cell body and cell body, or dendrite and dendrite. It is this functional contact that allows neurotransmission. Many neurologic and psychiatric diseases are caused by pathologic overactivity or underactivity of neurotransmission; and many drugs can modify neurotransmission, for examples hallucinogens, antipsychotics, anti-schizophrenia, tranquilizers, sedatives, anesthetics, pain drugs, Alzheimer's disease drugs, and Parkinson's disease drugs.
During recent years, a great deal of effort has been made by investigators to characterize the function of synaptic proteins, which include synaptotagmin, syntexin, synaptophysin, synaptobrevin, and the synapsins. These proteins are involved in specific aspects of synaptic function, e.g. synaptic vesicle recycling or docking, and in the organization of axonogenesis, differentiation of presynaptic terminals, and in the formation and maintenance of synaptic connections. See, for example, U.S. Patent Application Publication No. 2006/0019880.
Only by establishing synaptic connections can nerve cells organize into networks and acquire information processing capability such as learning and memory. Synapses are progressively reduced in number during normal aging, and are severely disrupted during neurodegenerative diseases. Therefore, finding molecules capable of creating and/or maintaining synaptic connections is an important step in the treatment of neurodegenerative diseases. Conversely, excessive synapse formation may be associated with stroke and psychiatric disorders. The modulation of synapse formation is of great interest for the treatment of a variety of nervous system disorders.
US 2006/0019880 discloses that thrombospondins can trigger synapse formation and a thrombospondin agonist or an antagonist can be used to promote or inhibit synaptogenesis in a patient in need of synaptogenesis promotion or inhibition.
All references, publications, and patent applications disclosed herein are hereby incorporated by reference in their entirety.